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Bioconjug Chem ; 21(5): 828-35, 2010 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-20387862

RESUMEN

Conjugates of 3-(1'-hexyloxyethyl)-3-devinyl pyropheophorbide-a (HPPH) with multiple Gd(III)aminobenzyl diethylenetriamine pentacetic acid (ADTPA) moieties were evaluated for tumor imaging and photodynamic therapy (PDT). In vivo studies performed in both mice and rat tumor models resulted in a significant MR signal enhancement of tumors relative to surrounding tissues at 24 h postinjection. The water-soluble (pH: 7.4) HPPH-3Gd(III) ADTPA conjugate demonstrated high potential for tumor imaging by MR and fluorescence. This agent also produced long-term tumor cures via PDT. An in vivo biodistribution study with the corresponding (14)C-analogue also showed significant tumor uptake 24 h postinjection. Toxicological evaluations of HPHH-3Gd(III)ADTPA administered at and above imaging/therapeutic doses did not show any evidence of organ toxicity. Our present study illustrates a novel approach for the development of water-soluble "multifunctional agents", demonstrating efficacy for tumor imaging (MR and fluorescence) and phototherapy.


Asunto(s)
Clorofila/análogos & derivados , Gadolinio/uso terapéutico , Neoplasias/diagnóstico , Neoplasias/tratamiento farmacológico , Animales , Clorofila/química , Clorofila/uso terapéutico , Fluorescencia , Gadolinio/química , Imagen por Resonancia Magnética/métodos , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C3H , Neoplasias/patología , Fotoquimioterapia/métodos , Ratas
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